Abstract 5251
Background
Prostate cancer (PCa) is one of the major cancers in men, but discrepancy between incidence and mortality calls for a careful approach to screening and diagnosis. Controversy between US Preventive Services Task Force recommendations and the outcomes clinical trials illustrate that the shortcomings of existing biomarkers and high demand in novel approaches for prostate cancer screening. Recent studies have suggested miRNAs as new candidates for cancer biomarkers. In this study, we have investigated the use of miRNAs found in cell-free nucleoprotein complexes and urine extracellular vesicles (EVs) as prostate cancer biomarkers.
Methods
Urine extracellular vesicles were isolated by standard ultracentrifugation protocols. Cell-free supernatant containing nucleoprotein complexes was obtained after 17.000g centrifugation. miRNA from supernatant and urine EVs were isolated as described previously (Lekchnov et al, Anal Biochem, 2016) and profiled using customized miRCURY LNA miRNA qPCR panels (Exiqon Ltd).
Results
Profiling of the expression of 84 miRNAs in paired samples of urine supernatant and urine EVs of 10 healthy donors (HD), 10 PCa patients and 10 patients with benign prostatic hyperplasia (BPH) has identified subsets of miRNAs differentially expressed between the groups. Using ratio-based normalization miRNA pairs with significantly different expression were selected and verified in an independent sample of 15 HD, 15 PCa and 15 BPH patients. To facilitate highly specific PCa detection a stepwise diagnostic algorithm based on miRNA expression in HD group (median ± 2SD cut off values) and hierarchical analysis of analytical systems was proposed (Bryzgunova et al, PLoS One, 2019). Diagnostic panels developed using miRNA profiling data and comprised of 24 miRNAs (17 miRNA ratios) could classify PCa and BPH patients and HD with 100% specificity and 97.5% accuracy. Diagnostic system based on the expression of 5 miRNA pairs in urine (miR-30a: miR-125b, miR-425: miR-331, miR-29b: miR-21, miR-191: miR-200a, miR-331: miR-106b) can be potentially used to identify PCa.
Conclusions
The data shows promise of urine cell-free and vesicle cargo miRNA as prostate cancer biomarkers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The study was supported by the Russian Science Foundation (no. 16-15-00124). Pavel P. Laktionov acknowledges financial support within the framework of the Russian state funded budget project # АААА-А17-117020210026-2 to the ICBFM SB RAS.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1267 - Genetic landscape of KEAP1 and NFE2L2 mutated cancers from the AACR GENIE database
Presenter: Mark Zaki
Session: Poster Display session 1
Resources:
Abstract
878 - β-arrestin1 is involved in the Ras-induced malignant transformation
Presenter: Takashi Shibano
Session: Poster Display session 1
Resources:
Abstract
4143 - Incidence of second cancer among PLWHIV: retrospective observational study of a series of 601 patients in the French CANCERVIH network
Presenter: Jean-Philippe Spano
Session: Poster Display session 1
Resources:
Abstract
5145 - A challenging task – Identifying carcinoma of unknown primary (CUP) patients according to ESMO guidelines: the CUPISCO trial experience
Presenter: Chantal Pauli
Session: Poster Display session 1
Resources:
Abstract
1737 - Incidence and Outcome of chronic lymphocytic leukemia with Deletion 17p: An Indian experience; challenges and opportunities
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
2596 - Driving solo? Investigation into collaborating mutations in SDH-deficient neoplasia
Presenter: Jonathan Killian
Session: Poster Display session 1
Resources:
Abstract
1499 - The potential of a novel antiangiogenic VEGFR1-D2 binding peptide in oncology therapeutics
Presenter: Afsaneh Sadre Momtaz
Session: Poster Display session 1
Resources:
Abstract
1775 - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors
Presenter: Mayu Yunokawa
Session: Poster Display session 1
Resources:
Abstract
4584 - First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumors: Dose-optimization cohorts
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract